Role of ATP-sensitive potassium channels in inhibitory effect of hydrogen sulfide on high glucose-induced inflammation mediated by necroptosis in H9c2 cardiac cells
10.3969/j.issn.1000-4718.2016.08.004
- VernacularTitle:ATP 敏感性钾通道在硫化氢抑制坏死性凋亡介导的高糖致 H9 c2心肌细胞炎症中的作用
- Author:
Weijie LIANG
;
Meiji CHEN
;
Jianhua HE
;
Wenzhu ZHANG
;
Fei CHENG
;
Jun LAN
;
Jianqiang FENG
;
Huimin HUANG
- Publication Type:Journal Article
- Keywords:
ATP-sensitive potassium channel;
Hydrogen sulfide;
Necroptosis;
High glucose;
Cardiomyocyte;
Inflammation
- From:
Chinese Journal of Pathophysiology
2016;32(8):1364-1369
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM:To investigate the role of ATP-sensitive potassium ( KATP ) channels in the inhibitory effect of hydrogen sulfide ( H2 S) on high glucose ( HG)-induced inflammation mediated by necroptosis in H 9c2 cardiac cells. METHODS:The expression levels of receptor-interacting protein 3 ( RIP3; an indicator of necroptosis ) and cyclooxyge-nase-2 (COX-2) were determined by Western blot.The levels of interleukin-1β(IL-1β) and tumor necrosis factor-α( TNF-α) were detected by ELISA .RESULTS:After H9c2 cardiac cells were treated with 35 mmol/L glucose ( HG) for 24 h, the expression of RIP3 was significantly increased .Pre-treatment of the cells with 100 μmol/L diazoxide ( DZ; a KATP channel opener) or 400 μmol/L NaHS (a donor of H2S) for 30 min considerably blocked the up-regulation of RIP3 induced by HG.Moreover, pre-treatment of the cells with 100 μmol/L 5-hydroxydecanoic acid (5-HD; a KATP channel
blocker) attenuated the inhibitory effect of NaHS on HG-induced up-regulation of RIP3.On the other hand, co-treatment of the cells with 100μmol/L necrostatin-1 ( a specific inhibitor of necroptosis ) or pre-treatment of the cells with 100 μmol/L DZ or 400 μmol/L NaHS attenuated HG-induced inflammatory responses , evidenced by decreases in the expression of COX-2 and secretion levels of IL-1βand TNF-α.However , pre-treatment of the cells with 100 μmol/L 5-HD significantly attenuated the above anti-inflammatory effects of NaHS.CONCLUSION:KATP channels play an important role in the inhib-itory effect of H2 S on HG-induced inflammation mediated by necroptosis in H 9c2 cardiac cells.